Integrated analysis of mRNA and lncRNA transcriptomes in peripheral blood of Holstein cattle at high and low altitudes

Abstract

Holstein cattle are selected for high milk yield but show limited adaptation to hypoxic environments. The transcriptional features underlying their long-term response to hypoxic stress, particularly the role of non-coding RNAs, remain poorly understood. This study analysed mRNA and long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from Holstein cows at high and low altitudes. In total, 7,625 differentially expressed genes (DEGs) and 4,956 differentially expressed lncRNAs (DELs) were identified. Functional enrichment analyses revealed significant downregulation of mitochondrial translation and oxidative phosphorylation pathways, alongside enrichment of immune-related processes among upregulated genes. Integrated analysis combining cis-acting positional evidence, WGCNA co-expression modules, and RNAplex thermodynamic filtering identified candidate lncRNA-mRNA co-expression associations. Core lncRNAs, including MSTRG.54387.36 (a cis-acting partner of CD274 ), were identified as RNAplex-supported targets with potential roles in hypoxia-associated immune modulation. This study characterises the transcriptomic response of Holstein cows to chronic hypoxia and identifies candidate mRNA-lncRNA co-expression associations. These findings lay the groundwork for future experimental dissection of altitude adaptation mechanisms.