The High Osmolarity Glycerol (HOG) signaling pathway is responsible for osmoregulation in fungi. Mutants with inactivated HOG-pathway are sensitive to osmotic stress. We found within this study several independent “loss-of-function” (lof)-mutants of the HOG-pathway in the filamentous rice blast fungus Magnaporthe oryzae to rapidly adapt osmoregulation upon permanent exposure to salt stress. Adaptation resulted in stable mutants being restored in osmoregulation arising as individuals outgrowing from salt-sensitive lof-mutants. We named these strains ?Mohog1(adapted), ?Mopbs2(adapted), ?Mossk2(adapted), ?Mossk1(adapted) and ?Moypd1(adapted). To identify potential genomic variations that resulted in the phenotypic variation in 'adapted' mutants, we have performed both DNA and RNA sequencing analyses. Next-generation sequencing analysis of RNA samples from the wildtype strain, ?Mohog1 and ?Mohog1(adapted) before and after 25 min salt stress (0.5 M KCl) gives insights into transcriptional changes which may be responsible for the adaptation phenomenon observed.