RNA-Seq reveals flight-induced changes in cerebellar transcriptomic profiles of racing pigeons.

The avian cerebellum is pivotal for multisensory integration and motor control during flight, yet its molecular adaptation to prolonged exertion remains incompletely defined. We profiled cerebellar transcriptomes of ten racing pigeons before and after a 300-km homing flight using whole-transcriptome RNA sequencing. Differential expression analysis revealed robust remodeling of metabolic and proteostatic pathways, including upregulation of SLC35D2, consistent with enhanced UDP-GlcNAc flux through the hexosamine biosynthetic pathway aligned with birds' naturally high glycaemia. Increased VLDLR expression links lipid handling to the reelin signalling cascade, suggesting contributions to navigation and synaptic plasticity, whereas downregulation of HTR1F indicates region-specific serotonergic modulation with exercise. Co-expression network analysis (WGCNA) identified modules enriched for endoplasmic reticulum protein processing and stress responses (PLAA, RAD23, ERN1), alongside intensified ribosome and RNA biogenesis, reflecting an elevated demand for protein synthesis and quality control. Functional enrichment (WebGestalt,) highlighted among others ribosome biogenesis, core metabolic pathways, RNA transport. These insights contribute to understanding the genetic and molecular mechanisms underpinning avian navigation and performance, providing a foundation for further research into flight-related neurophysiology.