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Simple Summary New free walk housing systems such as compost-bedded pack barns might positively influence animal welfare. However, udder health can be negatively affected due to the microbial environment in the pack. Udder health depends on many factors, such as the environment, the feed, the pathogen species, and the genetic mechanisms of the cow’s immune system. For a more precise evaluation of udder health, we examined novel traits including specific mastitis pathogens and differential somatic cell fractions in milk. In order to identify possible candidate genes for udder health, a genome-wide association study, including single-nucleotide polymorphisms (SNP) by housing system interactions (compost-bedded pack barn and conventional cubicle barn), was performed. We identified two potential candidate genes for the interaction effect in relation to udder health. The identified potential candidate gene HEMK1 (HemK methyltransferase family member 1) is involved in immune system development, and CHL1 (cell adhesion molecule L1 like) has an immunosuppressive effect during stress conditions. The results suggest housing system-specific breeding strategies in order to improve udder health in compost-bedded pack and conventional cubicle barns. Abstract The aim of the present study was to detect significant SNP (single-nucleotide polymorphism) effects and to annotate potential candidate genes for novel udder health traits in two different farming systems. We focused on specific mastitis pathogens and differential somatic cell fractions from 2198 udder quarters of 537 genotyped Holstein Friesian cows. The farming systems comprised compost-bedded pack and conventional cubicle barns. We developed a computer algorithm for genome-wide association studies allowing the estimation of main SNP effects plus consideration of SNPs by farming system interactions. With regard to the main effect, 35 significant SNPs were detected on 14 different chromosomes for the cell fractions and the pathogens. Six SNPs were significant for the interaction effect with the farming system for most of the udder health traits. We inferred two possible candidate genes based on significant SNP interactions. HEMK1 plays a role in the development of the immune system, depending on environmental stressors. CHL1 is regulated in relation to stress level and influences immune system mechanisms. The significant interactions indicate that gene activity can fluctuate depending on environmental stressors. Phenotypically, the prevalence of mastitis indicators differed between systems, with a notably lower prevalence of minor bacterial indicators in compost systems.