Breed-specific transcriptomic pathways underpin seasonal cold exposure responses in indigenous and crossbred cattle.

Livestock are essential to rural economies and livelihoods in emerging nations such as India, and reducing environmental impacts while sustaining economic returns is critical under ongoing climate change. This study aims to identify transcriptomic changes under cold (winter) and thermoneutral (spring) conditions in Indigenous (Tharparkar) and crossbred (Karan Fries) cattle using RNA-Seq analysis. A total of 6,537 differentially expressed genes were identified in Tharparkar cattle (471 upregulated, 6,066 downregulated) and 5,101 in Karan Fries (539 upregulated, 4,562 downregulated) using thresholds of log2 fold change ≥ 2 and p < 0.05. Expression changes in four selected genes were validated by real-time PCR. Functional enrichment analysis revealed significant upregulation of the Fc gamma R-mediated phagocytosis pathway in Tharparkar cattle and the N-glycan biosynthesis pathway in Karan Fries cattle; both cattle showed downregulation of the ECM-receptor interaction pathway and upregulation of the phagosome pathway under cold exposure. Many of the biological activities and molecular pathways linked to the differentially expressed genes were primarily associated with immune response, cellular signaling, and structural remodeling. PTPRC, MYC and CREB1 emerged as key regulator genes involved in multiple biological processes and signaling pathways in both cattle. These findings provide a robust framework for future research on livestock adaptation to climate change, and the identified pathways may serve as potential targets for climate-resilient breeding and management strategies aimed at improving cold tolerance in cattle.