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Aedes albopictus, also known as the Asian tiger mosquito, is indigenous to the tropical forests of Southeast Asia. Ae. albopictus is expanding across the globe at alarming rates, raising concern over the transmission of mosquito-borne diseases, such as dengue, West Nile fever, yellow fever, and chikungunya fever. Since Ae. albopictus was reported in Houston (Harris County, Texas) in 1985, this species has rapidly expanded to at least 32 states across the United States. Public health efforts aimed at controlling Ae. albopictus, including surveillance and adulticide spraying operations, occur regularly in Harris County. Despite rotation of insecticides to mitigate the development of resistance, multiple mosquito species including Culex quinquefasciatus and Aedes aegypti in Harris County show organophosphate and pyrethroid resistance. Aedes albopictus shows relatively low resistance levels as compared to Ae. aegypti, but kdr-mutation and the expression of detoxification genes have been reported in Ae. albopictus populations elsewhere. To identify potential candidate detoxification genes contributing to metabolic resistance, we used RNA sequencing of field-collected malathion-resistant and malathion-susceptible, and laboratory-maintained susceptible colonies of Ae. albopictus by comparing the relative expression of transcripts from three major detoxification superfamilies involved in malathion resistance due to metabolic detoxification. Between these groups, we identified 12 candidate malathion resistance genes and among these, most genes correlated with metabolic detoxification of malathion, including four P450 and one alpha esterase. Our results reveal the metabolic detoxification and potential cuticular-based resistance mechanisms associated with malathion resistance in Ae. albopictus in Harris County, Texas. Author summary: The Asian tiger mosquito, Aedes albopictus, is an invasive species rapidly expanding worldwide. It is the main vector for several arboviruses, including dengue virus, Zika virus, and chikungunya virus. These viral diseases pose a substantial threat to global public health. Ae. albopictus has developed resistance to insecticides such as malathion, making its control more challenging. To uncover the genetic basis of this resistance, we conducted a study using RNA sequencing-based transcriptome profiling. In this study, we obtained gene expression patterns in malathion-resistant and susceptible mosquitoes. The transcriptomic information allowed us to identify potential key genes in detoxification gene families associated with metabolic resistance to malathion. Our discovery provides insights into the molecular mechanisms behind malathion resistance in Ae. albopictus. Our research not only contributes to the understanding of mosquito biology and control but also highlights the future direction for continued efforts in developing innovative strategies to mitigate rapid development of insecticide resistance in Ae. albopictus. [ABSTRACT FROM AUTHOR]