Fungi are recognized as indigenous microbes in natural hypersaline habitats. Aspergillus sp, among other fungi, is predominant in those environments; however, their adaptative abilities are recently studied. This study analyzes the transcriptomic response of an obligate halophile Aspergillus loretoensis under two salinity conditions (4% and 15% NaCl). This fungus shows stress under the low NaCl concentration tested since it overexpresses genes like SOD2 (oxidative stress and oxygen toxicity), ASG (resistance to salinity), and transmembrane transport (ZRT2, OAC1, PMA1, ZRC1, SNQ2, MCH4, YO075, SIT1). Meanwhile, at 15% NaCl, the up-regulated genes at 15% NaCl were related to osmolytes transport (STL1, HXT13, ZRT1), carbohydrate transport, and metabolism (MAL11, PK1, ITR1), all suggesting their adaptive conditions. This fungus expresses interesting metabolic enzymes with potential uses in biotechnology as invertases, isomerases, maltases, and lipases. As well it showed biosynthetic pathways related to oil degradation and antibiotic production.