Comparative Skin Transcriptome Analysis Identifies Candidate Genes Associated with Skin Responses in Hu Sheep Raised Under Different Regional Rearing Conditions

To identify candidate genes associated with skin tissue responses in Hu sheep raised under different regional rearing environments and to preliminarily explore their potential relevance to low-temperature-related environmental responses, this study used 1-year-old female Hu sheep raised in Anhui and Xinjiang as the experimental animals. Skin tissues were collected from the left scapular region, and their transcriptomic profiles were characterized by integrating histological analysis, RNA sequencing (RNA-seq), differential expression analysis, functional enrichment analysis, protein–protein interaction (PPI) network construction, and RT-qPCR validation. The results showed significant differences between the two groups in body weight, body length, body height, cannon circumference, rectal temperature, and ear temperature. Hematoxylin and eosin (H&E) staining indicated that the Xinjiang group exhibited a denser distribution of hair follicles, a relatively thicker dermis, and a more compact arrangement of collagen fibers, suggesting enhanced insulation-related skin characteristics. Transcriptome sequencing identified 295 differentially expressed genes (DEGs), including 193 upregulated and 102 downregulated genes. GO and KEGG enrichment analyses showed that these DEGs were mainly involved in immune and inflammatory responses, redox processes, extracellular matrix remodeling, and lipid and energy metabolism-related pathways, with significant enrichment in cytokine–cytokine receptor interaction, the chemokine signaling pathway, the NF-κB signaling pathway, glutathione metabolism, and drug metabolism–cytochrome P450. By further integrating PPI network analysis and functional annotation, CXCL13, CCL2, FGF21, GPX3, CYP1A1, HSD11B1, CDO1, and STEAP4 were identified as candidate genes. RT-qPCR results showed that the expression trends of the selected genes were generally consistent with the RNA-seq results. Overall, this study revealed differences in phenotypic traits, skin histological structure, and transcriptomic characteristics between Hu sheep raised in different regions, providing preliminary molecular clues potentially associated with low-temperature-related environmental responses. Given the differences in geographic origin and rearing environments between the two groups, the findings should be interpreted as associative evidence of skin transcriptomic responses in Hu sheep under different environmental conditions—rather than as direct causal evidence that low temperature alone drove these transcriptomic differences.