LAUSR

Abstract Species are facing strong selection pressures to adapt to inhospitable high-altitude environments. Yaks are a valuable species and an iconic symbol of the Qinghai-Tibet Plateau. Extensive studies of high-altitude adaptation have been conducted, but few have focused on metabolism. In the present study, we determined the differences in the serum metabolomics between yaks and the closely related species of low-altitude yellow cattle and dairy cows. We generated high-quality metabolite profiling data for 36 samples derived from the three species, and a clear separation trend was obtained between yaks and the other animals from principal component analysis. In addition, we identified a total of 63 differentially expressed metabolites among the three species. Functional analysis revealed that differentially expressed metabolites were related to the innate immune activation, oxidative stress-related metabolism, and energy metabolism in yaks, which indicates the important roles of metabolites in high-altitude adaptation in yaks. The results provide new insights into the mechanism of adaptation or acclimatization to high-altitude environments in yaks and hypoxia-related diseases in humans.