<p>Long-term space flights induce adaptive changes in almost all tissues and organs. To elucidate adaptive mechanisms at the molecular and cellular levels, it is important to analyze transcriptional shifts in response to weightlessness/microgravity. Here we examined the transcriptomic profile of mouse lung tissue after a long-term space mission as part of the NASA Rodent Research scientific program. We identified 45 differentially expressed genes. G-protein-coupled olfactory and vomeronasal receptor encoding genes were found to be “ectopically” upregulated. Most of the downregulated genes are responsible for protein folding and regulation of circadian rhythms. The obtained data confirm the low level of gravity sensitivity of lung cells and their high adaptive potential under conditions of prolonged space flight.</p>