Exploring transcriptomic mechanisms underlying pulmonary adaptation to diverse environments in Indian rams

Background: The Changthangi sheep thrive at high altitudes in the cold desert regions of Ladakh, India while Muzaffarnagri sheep are well-suited to the low altitude plains of northern India. This study investigates the molecular mechanisms of pulmonary adaptation to diverse environments by analyzing gene expression profiles of lung tissues through RNA sequencing. Methods and results: Four biological replicates of lung tissue from each breed were utilized to generate the transcriptomic data. Differences in gene expression analysis revealed discrete expression profiles in lungs of each breed. In Changthangi sheep, genes related to immune responses, particularly cytokine signaling, were significantly enriched. Pathway analysis highlighted the activation of NF-kB signaling, a key mediator of inflammation and immune response. Additionally, the gene network analysis indicated a strong association between cytokine signaling, hypoxia-inducible factor (HIF) and NF-kB activation, suggesting a coordinated response to hypoxic stress in lungs of Changthangi sheep. In Muzaffarnagri sheep, the gene expression profiles were enriched for pathways related to energy metabolism, homeostasis and lung physiology. Key pathways identified include collagen formation and carbohydrate metabolism, both of which are crucial for maintaining lung function and structural integrity. Gene network analysis further reinforced this by revealing a strong connection between genes associated with lung structure and function. Conclusions: Our findings shed light on the valuable insights into gene expression mechanisms that enable these sheep breeds to adapt to their respective environments and contribute to a better understanding of high altitude adaptation in livestock.