ABSTRACT: No major transcriptomic differences were observed between JPR-R1/2 and JPR when strains were not exposed to pyflubumide. Only three genes (tetur13g01730, tetur14g03160, and tetur14g01700) were consistently up-regulated in JPR-R1/2, but none coded for enzymes that are known to be associated with xenobiotic metabolism. As a next step, we used the original and susceptible JPO strain, the parent of JPR, as a reference to investigate transcriptomic changes. Compared to JPO, 16 cytochrome P450s were up-regulated in JPR, whereas two CCE genes were down-regulated. In both JPR-R1/2, 13 cytochrome P450s were up-regulated compared to JPO, of which 11 genes already showed significant up-regulation in JPR (CYP392D2, CYP392D6, and CYP392E8 had the highest average transcriptional increase). As only limited constitutive gene expression differences were observed between JPR and the JPR-R1/2 strains, the plastic, environmentally dependent, transcriptomic changes were characterized to shed light on the molecular basis of pyflubumide resistance. After nine hours of exposure to a non-lethal dose of pyflubumide (100 mg/L), no DEGs were detected in JPR-R1 upon pyflubumide exposure, whereas only a single DEG (tetur04g04350, log2FC of 1.17) was observed in JPR. After 24 hours of exposure to pyflubumide (100mg/L), large transcriptomic responses were observed in JPR-R1/2. Eight cytochrome P450s were part of the positively correlated response, of which five (CYP385C4, CYP385C4v2, CYP392D2, CYP392E8, and CYP392A4) showed up-regulation after exposure to pyflubumide.