Elephant seals exhibit extreme behaviors characterized by sustained exposure to glucocorticoids, but the mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, imaging, and functional analyses to explore the mechanisms that underlie tolerance to glucocorticoids in elephant seal muscle cells. Elephant seal muscle progenitor cells differentiated into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to the glucocorticoid dexamethasone at three ascending doses (0.1, 1, and 100uM) for 48h resulted in concerted changes in expression of 6 clusters of genes related to the structural constituents of muscle and pathways associated with energy metabolism and cell survival. Sustained exposure to glucocorticoids also promoted mitochondrial fission, dissociation of mitochondria-ER interactions, reduced oxygen consumption rates (OCR), and a shift of metabolic phenotype towards glycolysis. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses of catabolic and muscle structural genes corroborated that the observed effects are mediated by GR signaling. Knockdown of the GR-regulated stress gene ddit4 recovered OCR and upregulated genes involved in redox balance. Overall, these results show that adaptation to sustained glucocorticoid exposure in elephant seal muscle cells involves changes the mitochondrial reticulum and mitochondria-ER interactions, which support a reduction in mitochondrial metabolism promoting cell survival.