Background: The sedentary root-knot nematode Meloidogyne spp. secretes effectors in a spatial and temporal manner to interfere with and mimic multiple physiological and morphological mechanisms, supporting construction and maintenance of nematodes' feeding sites. For successful parasitism, many effectors act as immunomodulators, aimed to manipulate and suppress immune defense signaling triggered upon nematode invasion. Results: Comprehensive oxylipin profiling of tomato roots, performed using LC–MS/MS, indicated a sharp fluctuation in oxylipin profile following Root Knot Nematode infection. To identify genes that might respond to the lipidomic defense pathway mediated through oxylipins, RNA-Seq was performed by exposing Meloidogyne javanica second-stage juveniles to tomato protoplasts and the oxylipin 9-HOT, early induced in tomato roots upon nematode infection. A total of 4810 differentially expressed genes were identified. To target putative effectors, we explored differentially expressed genes carrying a predicted secretion signal peptide. Among these, several were homologous with known effectors in other nematode species; other unknown, potentially secreted proteins may have a role as root-knot nematode effectors that are induced by plant lipid signals. These include effectors functioning in the manipulation of plant defense signaling and root lipidomics, cell-wall weakening, detoxifying the stressful environment at the plant-nematode interface, allowing feeding site construction and development. Conclusions: Being an integral part of the plant's defense response, oxylipins may play an important signaling role in the regulation of nematode effectors. Herein we uncover activation of specific oxylipins signaling pathways upon nematode infection, which in turn
result in reprogramming the nematode effector repertoires responsible for promotion of feeding site construction and nematode parasitism.