Abstract
This study investigates the mechanisms underlying drought adaptability in Duolang sheep, a local breed from two distinct habitats in Xinjiang-an arid southern region and a grassland northern region-aiming to identify key factors driving differential environmental adaptation. Integrated multi-omics analyses were performed, including serum biochemical assays, untargeted metabolomics of perirenal and tail fat tissues, and transcriptomic profiling of lung, liver, and kidney samples. Our results revealed notable differences: (1) serum levels of GSH-Px, IL-2, and IgG were significantly higher in the southern group (p < 0.01); (2) metabolomic analysis identified key differential metabolites, including EPA (involved in unsaturated fatty acid biosynthesis), choline (glycerophospholipid metabolism), L-serine and glutathione (cofactor biosynthesis), and taurine (sulfur metabolism); and (3) transcriptomic analysis revealed significant differential expression of genes such as FGF21 (thermogenesis), CD14 and DUSP2 (MAPK signaling pathway), GOT1 (arginine biosynthesis), and AVPR2 (vasopressin-regulated water reabsorption). Integrative correlation analysis further indicated that glutathione, EPA, GOT1, and CD14 are involved in energy and lipid metabolism, while taurine, AVPR2, and DUSP2 contribute to oxidative stress resistance and immune regulation. These molecular and metabolic adjustments collectively enhance drought adaptability in southern Xinjiang Duolang sheep. In conclusion, adaptation to arid environments requires enhanced antioxidant capacity and immune function, with metabolites such as EPA supporting lipid metabolism and genes such as FGF21 regulating fatty acid oxidation to limit triglyceride accumulation.