As modern genomic tools are developed for ecologically compelling models, field manipulation experiments will become important for establishing the role of functional genomic variation in physiological acclimation and evolutionary adaptation along environmental clines. High-altitude habitats expose individuals to hypoxic and thermal stress, necessitating physiological acclimation, which may result in evolutionary adaptation. We assayed skeletal muscle transcriptomic profiles of rufous-collared sparrows (Zonotrichia capensis) distributed along an altitudinal gradient on the Pacific slope of the Peruvian Andes. Nearly 200 unique transcripts were differentially expressed between high-altitude [4100 m above sea level (a.s.l.)] and low-altitude (2000 m a.s.l.) populations in their native habitats. Gene ontology and network analyses revealed that these transcripts are primarily involved in oxidative phosphorylation, protein biosynthesis, signal transduction and oxidative stress response pathways. To assess the plasticity in gene expression differences between populations, we performed a ‘common garden’ experiment in which high- and low-altitude individuals were transferred to a common low-altitude site (~150 m). None of the genes that were differentially expressed between populations at the native altitudes remained significantly different between populations in the common garden. The role of gene expression variation in adaptation and acclimation to environmental stress is largely unexplored in natural populations of birds. These results demonstrate substantial plasticity in the biochemical pathways that underpin cold and hypoxia compensation in Z. capensis, which may mechanistically contribute to enabling the broad altitudinal distribution of the species.