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Introduction: Long-term domestication in high-altitude environments has led to unique changes in the gut microbiota of Tibetan Pigs. This study aims to investigate specific alterations in the intestinal flora of Tibetan Pigs compared to Yorkshire pigs. Methods: We employed 16S rRNA and metagenomic sequencing technologies for comprehensive analysis of the gut microbiota. The data collected allowed us to assess microbial community structures and functional capabilities. Results: Our analysis revealed that Tibetan Pigs raised under a "free-range + supplementary feeding" model exhibited increased abundance of microbial communities associated with short-chain fatty acid synthesis and the digestion of cellulose and hemicellulose. Notably, the characteristic bacterium Rhodococcus , commonly found in high-altitude environments, was enriched in the gut microbiota of Tibetan Pigs, facilitating the efficient utilization of natural compounds and degradation of toxic substances. Additionally, the increased abundance of probiotics in these pigs enhances their immunity, which may involve mechanisms such as disrupting the structure of pathogenic bacteria and detoxifying harmful metabolites. Discussion: These findings underscore the advantages of Tibetan Pigs over common commercial breeds, highlighting their unique gut microbiota adaptations. Furthermore, they open new avenues for screening potential probiotics and developing genetic breeding strategies for improved livestock varieties. Conclusion: Understanding the distinct gut microbiota of Tibetan Pigs provides valuable insights into their health benefits and resilience, contributing to future research on breed improvement and microbiome applications in agriculture. [ABSTRACT FROM AUTHOR]

The high-altitude, low-oxygen environment of the Qinghai-Tibet Plateau poses significant challenges for the introduction of superior livestock breeds. However, local plateau species have adapted to thrive and reproduce under these harsh conditions. Understanding the molecular mechanisms behind plateau animals' adaptation to low-oxygen environments is essential for breeding livestock suited to high-altitude regions. Tibetan pigs, which have undergone long-term natural selection and artificial breeding, have developed the ability to survive and reproduce in hypoxic environments. In this study, we conducted whole-genome resequencing of 30 Tibetan pigs from high-altitude regions and 30 Diannan small-ear pigs from low-altitude areas, to identify candidate genes that support Tibetan pigs' adaptation to hypoxic conditions through selection signal analysis. Additionally, we performed transcriptome sequencing on five tissues (heart, liver, spleen, lung, and bone marrow) from both Tibetan pigs and Diannan small-ear pigs to identify genes with significant differential expression between the two breeds. We then integrated the genomic and transcriptomic data by examining the expression of candidate genes identified in selection signal analysis across different tissues. The selection signal analysis identified 10 genes— HES 4, ANGPT 1, HIF3 A, SPHK 2, PCK 2, RCN 3, HIGD2 A, DNM 2, IRF 9, and SRF —that were under positive selection in the Tibetan pig population and are associated with hypoxia adaptation. When combined with transcriptome data, we found that five of these genes— HIF3 A, RCN 3, HIGD2 A, PCK 2, and IRF 9—exhibited differential expression. Through an integrated approach of selection signal and transcriptome analysis, we identified five key functional genes that contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings offer new insights into the adaptability of plateau animals. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria is an important dominant bacterial community in the intestinal tract, which can regulate the intestinal environment and maintain the balance of intestinal flora. However, there are few studies on Tibetan pig lactic acid bacteria. The purpose of this study was to isolate and identify lactic acid bacteria from Tibetan pig feces, and to provide experimental materials for the development and utilization of Tibetan pig probiotics. Seventeen strains of Lactobacillus isolated from Tibetan pig manure were identified by physiology, biochemistry, 16S rRNA molecular biology and acid and bile salt tolerance tests. The results showed that, screened strain is Lactobacillus Roy’s F1. Tibetan pig source Roy’s Lactobacillus F1 showed the ability to grow maximum when the inoculation was 1%, the temperature 37 ℃ and pH = 7. This strain depicted a strong tolerance for artificial gastric and intestinal juice. Roy’s Lactobacillus F1 can inhibit the growth of Staphylococcus aureus and Salmonella. Lactobacillus reuteri F1 also showed a strong hydrophobicity and self-agglutination ability. It is sensitive to butamicane, chloramphenicol, erythromycin, cefazolin, norfloxacin, cotrimoxazole and other antibiotics, and has resistance for ampicillin, gentamicin, ciprofloxacin, penicillin and so on. In this study, one strain of Tibetan Porcine Lactobacillus was screened, obtained, and its biological characteristics were found good, which could provide reference and support for the development and utilization of Tibetan porcine probiotics. [ABSTRACT FROM AUTHOR]

Simple Summary: The problem of low fertility in Tibetan pigs has a long history. In order to solve the problem of low fertility in Tibetan pigs, in this study, we successfully constructed cDNA libraries of the transcriptome from ovarian tissues of Tibetan and Yorkshire pigs using RNA-Seq technology, analyzed and screened the genes significantly enriched in the pathways closely related to the regulation of reproduction, and finally identified AR, CYP11A1, CYP17A1, INHBA, ARRB2, EGFR, ETS1, HSD17B1, IGF1R, MIF, SCARB1, and SMAD4 as important candidate genes. The 12 differentially expressed genes screened in relation to reproduction were validated using RT-qPCR. The results showed that six genes were highly significantly (p < 0.01) higher in expression in Tibetan pigs than in Yorkshire pigs, i.e., AR, CYP17A1, EGFR, ETS1, IGF1R, and SMAD4; on the other hand, six genes were highly significantly (p < 0.01) lower in expression in Tibetan pigs than in Yorkshire pigs, i.e., CYP11A1, INHBA, ARRB2, HSD17B, MIF, SCARB1. This study provides a theoretical basis for improving the regulatory genes in Tibetan pigs. The purpose of this study was to explore and verify genes that regulate the reproductive traits of Tibetan pigs at the mRNA level. The ovarian tissues of Tibetan pigs (TPs) and Yorkshire pigs (YPs) were selected as research objects, and cDNA libraries of the ovarian tissue transcripts of Tibetan pigs and Yorkshire pigs were successfully constructed by the RNA-Seq technique. A total of 651 differentially expressed genes (DEGs) were screened, including 414 up-regulated genes and 237 down-regulated genes. Through GO and KEGG enrichment analysis, it was found that these differentially expressed genes were significantly enriched in cell process, reproductive process, reproduction, cell proliferation, binding, and catalytic activity, as well as oxidative phosphorylation, endocrine resistance, thyroid hormone, Notch, and other signal transduction pathways. Genes significantly enriched in pathways closely related to reproductive regulation were analyzed and selected, and the AR, CYP11A1, CYP17A1, INHBA, ARRB2, EGFR, ETS1, HSD17B1, IGF1R, MIF, SCARB1, and SMAD4 genes were identified as important candidate genes. Twelve differentially expressed genes related to reproduction were verified by RT-qPCR. The results showed that the expression of the AR, CYP17A1, EGFR, ETS1, IGF1R, and SMAD4 genes was significantly higher in Tibetan pigs than in Yorkshire pigs, while the expression of the CYP11A1, INHBA, ARRB2, HSD17B, MIF, and SCARB1 genes in Tibetan pigs was significantly lower than in Yorkshire pigs. The purpose of this study is to provide a theoretical basis for exploring the molecular mechanism of reproductive trait effect genes and the application of molecular breeding in Tibetan pigs. [ABSTRACT FROM AUTHOR]

IntroductionLong-term domestication in high-altitude environments has led to unique changes in the gut microbiota of Tibetan Pigs. This study aims to investigate specific alterations in the intestinal flora of Tibetan Pigs compared to Yorkshire pigs.MethodsWe employed 16S rRNA and metagenomic sequencing technologies for comprehensive analysis of the gut microbiota. The data collected allowed us to assess microbial community structures and functional capabilities.ResultsOur analysis revealed that Tibetan Pigs raised under a “free-range + supplementary feeding” model exhibited increased abundance of microbial communities associated with short-chain fatty acid synthesis and the digestion of cellulose and hemicellulose. Notably, the characteristic bacterium Rhodococcus, commonly found in high-altitude environments, was enriched in the gut microbiota of Tibetan Pigs, facilitating the efficient utilization of natural compounds and degradation of toxic substances. Additionally, the increased abundance of probiotics in these pigs enhances their immunity, which may involve mechanisms such as disrupting the structure of pathogenic bacteria and detoxifying harmful metabolites.DiscussionThese findings underscore the advantages of Tibetan Pigs over common commercial breeds, highlighting their unique gut microbiota adaptations. Furthermore, they open new avenues for screening potential probiotics and developing genetic breeding strategies for improved livestock varieties.ConclusionUnderstanding the distinct gut microbiota of Tibetan Pigs provides valuable insights into their health benefits and resilience, contributing to future research on breed improvement and microbiome applications in agriculture.

The high-altitude, low-oxygen environment of the Qinghai-Tibet Plateau poses significant challenges for the introduction of superior livestock breeds. However, local plateau species have adapted to thrive and reproduce under these harsh conditions. Understanding the molecular mechanisms behind plateau animals’ adaptation to low-oxygen environments is essential for breeding livestock suited to high-altitude regions. Tibetan pigs, which have undergone long-term natural selection and artificial breeding, have developed the ability to survive and reproduce in hypoxic environments. In this study, we conducted whole-genome resequencing of 30 Tibetan pigs from high-altitude regions and 30 Diannan small-ear pigs from low-altitude areas, to identify candidate genes that support Tibetan pigs’ adaptation to hypoxic conditions through selection signal analysis. Additionally, we performed transcriptome sequencing on five tissues (heart, liver, spleen, lung, and bone marrow) from both Tibetan pigs and Diannan small-ear pigs to identify genes with significant differential expression between the two breeds. We then integrated the genomic and transcriptomic data by examining the expression of candidate genes identified in selection signal analysis across different tissues. The selection signal analysis identified 10 genes—HES4, ANGPT1, HIF3A, SPHK2, PCK2, RCN3, HIGD2A, DNM2, IRF9, and SRF—that were under positive selection in the Tibetan pig population and are associated with hypoxia adaptation. When combined with transcriptome data, we found that five of these genes—HIF3A, RCN3, HIGD2A, PCK2, and IRF9—exhibited differential expression. Through an integrated approach of selection signal and transcriptome analysis, we identified five key functional genes that contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings offer new insights into the adaptability of plateau animals.

Tibetan pig is a unique pig breed native to the Qinghai–Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals. [ABSTRACT FROM AUTHOR]

Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai–Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions. [ABSTRACT FROM AUTHOR]

【Objective】In mammals, Toll-like receptors and antimicrobial peptide genes are important components of the innate immune system, which play a crucial role in fighting against pathogen attacks. The study was conducted to explore the expression differences of Toll-like receptor and antimicrobial peptide genes between different immune organs or tissues in Tibetan pigs and Duroc-Landrace-Yorkshire pigs, with an aim to reveal the potential contribution of these genes to disease resistance and immune response and provide theoretical support for the screening of molecular markers for disease resistance.【Method】The mRNA abundance of Toll-like receptors genes (TLR1-TLR9) and two types of antimicrobial peptide genes (PBD-1 and PR-39) in lungs, mesenteric lymph nodes, inguinal lymph nodes, submandibular lymph nodes and spleens of 6-month-old Tibetan and Duroc-Landrace-Yorkshire pigs were detected by qPCR.【Result】The mRNA expression of Tolllike receptors and antimicrobial peptide genes in most of the immune organs or tissues of Tibetan pigs was significantly higher than that of Duroc-Landrace-Yorkshire pigs. Among them, the mRNA expression of TLR1 and TLR2 in lungs was increased by about 50%, and PR-39 was increased by 2.6 times; the expression of TLR4 in mesenteric lymph nodes was increased by 40%, and the expression of TLR1 and PR-39 was increased by 88% and 3 times, respectively. In the inguinal lymph nodes, the expression of TLR1 and TLR2 was increased by about 2 times, and the expression of TLR9 and PR-39 was increased by 70%, especially, the expression of PR-39 increasing by 7 times; The expression of TLR1, TLR2, TLR4 and TLR7 in submandibular lymph nodes was increased by more than 2 times, and the expression of PR-39 was increased by nearly 7 times, which was similar to that in inguinal lymph nodes; the expression of TLR1 in the spleen rose by 3.5 times, which was similar to that in submandibular lymph nodes. The expression of TLR4 and TLR9 increased by about 50%, and the expression of PR-39 increased by 2.5 times.【Conclusion】Tibetan pigs show higher expression levels of Toll-like receptors and antimicrobial peptide genes in multiple immune organs or tissues compared to Duroc-Landrace-Yorkshire pigs. It is implied that Tibetan pigs may possess stronger innate immunity and be able to generate more effective local or systemic immune responses against pathogenic microbial infections. The results of this study provide important theoretical support for the identification of disease resistance molecular markers and are expected to provide a scientific basis for further improvement of disease resistance in Tibetan pigs and other pig breeds.

【Objective】In mammals, Toll-like receptors and antimicrobial peptide genes are important components of the innate immune system, which play a crucial role in fighting against pathogen attacks. The study was conducted to explore the expression differences of Toll-like receptor and antimicrobial peptide genes between different immune organs or tissues in Tibetan pigs and Duroc-Landrace-Yorkshire pigs, with an aim to reveal the potential contribution of these genes to disease resistance and immune response and provide theoretical support for the screening of molecular markers for disease resistance. 【Method】The mRNA abundance of Toll-like receptors genes (TLR1-TLR9) and two types of antimicrobial peptide genes (PBD-1 and PR-39) in lungs, mesenteric lymph nodes, inguinal lymph nodes, submandibular lymph nodes and spleens of 6-month-old Tibetan and Duroc-Landrace-Yorkshire pigs were detected by qPCR.【Result】The mRNA expression of Tolllike receptors and antimicrobial peptide genes in most of the immune organs or tissues of Tibetan pigs was significantly higher than that of Duroc-Landrace-Yorkshire pigs. Among them, the mRNA expression of TLR1 and TLR2 in lungs was increased by about 50%, and PR-39 was increased by 2.6 times; the expression of TLR4 in mesenteric lymph nodes was increased by 40%, and the expression of TLR1 and PR-39 was increased by 88% and 3 times, respectively. In the inguinal lymph nodes, the expression of TLR1 and TLR2 was increased by about 2 times, and the expression of TLR9 and PR-39 was increased by 70%, especially, the expression of PR-39 increasing by 7 times; The expression of TLR1, TLR2, TLR4 and TLR7 in submandibular lymph nodes was increased by more than 2 times, and the expression of PR-39 was increased by nearly 7 times, which was similar to that in inguinal lymph nodes; the expression of TLR1 in the spleen rose by 3.5 times, which was similar to that in submandibular lymph nodes. The expression of TLR4 and TLR9 increased by about 50%, and the expression of PR-39 increased by 2.5 times.【Conclusion】Tibetan pigs show higher expression levels of Toll-like receptors and antimicrobial peptide genes in multiple immune organs or tissues compared to Duroc-Landrace-Yorkshire pigs. It is implied that Tibetan pigs may possess stronger innate immunity and be able to generate more effective local or systemic immune responses against pathogenic microbial infections. The results of this study provide important theoretical support for the identification of disease resistance molecular markers and are expected to provide a scientific basis for further improvement of disease resistance in Tibetan pigs and other pig breeds. [ABSTRACT FROM AUTHOR]

Simple Summary: Modern agricultural methods have led to the introduction of normally highland Tibetan pigs to lowland areas because of their high-quality meat. Similar to humans, indigenous Tibetan pigs residing in high-altitude regions may develop high-altitude de-acclimatization syndrome when exposed to low-altitude environments. Thus, it is important to better understand the low-altitude adaptation mechanisms of Tibetan pigs. We performed a comparative analysis between highland and lowland Tibetan pigs using genotyping data to investigate their genetic differences. Our results showed that immune-related genes were selected in highland Tibetan pigs, whereas genes associated with reproduction, growth and development, and blood pressure regulation were selected in lowland Tibetan pigs. These findings will contribute to research into the genetic basis of environmental adaptation and important economic traits in Tibetan pigs and provide genetic targets for breeding programs to improve Tibetan pigs. Tibetan pigs are indigenous to the Qinghai–Tibet Plateau and have been the subject of extensive genomic research primarily focused on their adaptation to high altitudes. However, genetic modifications associated with their response to low-altitude acclimation have not been thoroughly explored. To investigate the genetic basis underlying the low-altitude acclimation of Tibetan pigs, we generated and analyzed genotyping data of Tibetan pigs that inhabit high-altitude regions (average altitude 4000 m) and Tibetan pigs that have inhabited nearby low-altitude regions (average altitude 500 m) for approximately 20 generations. We found that the highland and lowland Tibetan pigs have distinguishable genotype and phenotype variations. We identified 46 and 126 potentially selected SNPs associated with 29 and 56 candidate genes in highland and lowland Tibetan pigs, respectively. Candidate genes in the highland Tibetan pigs were involved in immune response (NFYC and STAT1) and radiation (NABP1), whereas candidate genes in the lowland Tibetan pigs were related to reproduction (ESR2, DMRTA1, and ZNF366), growth and development (NTRK3, FGF18, and MAP1B), and blood pressure regulation (CARTPT). These findings will help to understand the mechanisms of environmental adaptation in Tibetan pigs and offer valuable information into the genetic improvement of Tibetan pigs pertaining to low-altitude acclimation and economic traits. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore and verify genes that regulate the reproductive traits of Tibetan pigs at the mRNA level. The ovarian tissues of Tibetan pigs (TPs) and Yorkshire pigs (YPs) were selected as research objects, and cDNA libraries of the ovarian tissue transcripts of Tibetan pigs and Yorkshire pigs were successfully constructed by the RNA-Seq technique. A total of 651 differentially expressed genes (DEGs) were screened, including 414 up-regulated genes and 237 down-regulated genes. Through GO and KEGG enrichment analysis, it was found that these differentially expressed genes were significantly enriched in cell process, reproductive process, reproduction, cell proliferation, binding, and catalytic activity, as well as oxidative phosphorylation, endocrine resistance, thyroid hormone, Notch, and other signal transduction pathways. Genes significantly enriched in pathways closely related to reproductive regulation were analyzed and selected, and the AR, CYP11A1, CYP17A1, INHBA, ARRB2, EGFR, ETS1, HSD17B1, IGF1R, MIF, SCARB1, and SMAD4 genes were identified as important candidate genes. Twelve differentially expressed genes related to reproduction were verified by RT-qPCR. The results showed that the expression of the AR, CYP17A1, EGFR, ETS1, IGF1R, and SMAD4 genes was significantly higher in Tibetan pigs than in Yorkshire pigs, while the expression of the CYP11A1, INHBA, ARRB2, HSD17B, MIF, and SCARB1 genes in Tibetan pigs was significantly lower than in Yorkshire pigs. The purpose of this study is to provide a theoretical basis for exploring the molecular mechanism of reproductive trait effect genes and the application of molecular breeding in Tibetan pigs.

Tibetan pig is a unique pig breed native to the Qinghai–Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals.

Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai–Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions.

Tibetan pigs are indigenous to the Qinghai–Tibet Plateau and have been the subject of extensive genomic research primarily focused on their adaptation to high altitudes. However, genetic modifications associated with their response to low-altitude acclimation have not been thoroughly explored. To investigate the genetic basis underlying the low-altitude acclimation of Tibetan pigs, we generated and analyzed genotyping data of Tibetan pigs that inhabit high-altitude regions (average altitude 4000 m) and Tibetan pigs that have inhabited nearby low-altitude regions (average altitude 500 m) for approximately 20 generations. We found that the highland and lowland Tibetan pigs have distinguishable genotype and phenotype variations. We identified 46 and 126 potentially selected SNPs associated with 29 and 56 candidate genes in highland and lowland Tibetan pigs, respectively. Candidate genes in the highland Tibetan pigs were involved in immune response (NFYC and STAT1) and radiation (NABP1), whereas candidate genes in the lowland Tibetan pigs were related to reproduction (ESR2, DMRTA1, and ZNF366), growth and development (NTRK3, FGF18, and MAP1B), and blood pressure regulation (CARTPT). These findings will help to understand the mechanisms of environmental adaptation in Tibetan pigs and offer valuable information into the genetic improvement of Tibetan pigs pertaining to low-altitude acclimation and economic traits.