AbstractThe pathogen Spongospora subterranea infects potato roots and developing tubers resulting in tuber yield and quality losses. Currently, there are no fully effective treatments for disease control. Host resistance is an important tool in disease management and understanding the molecular mechanisms of defence responses in roots of potato plants is required for the breeding of novel resistant cultivars. Here, we integrated transcriptomic and proteomic datasets to uncover these mechanisms underlying S. subterranea resistance in potato roots. This multi-omics approach identified upregulation of glutathione metabolism at the levels of RNA and protein in the resistant cultivar but not in the susceptible cultivar. Upregulation of the lignin metabolic process, which is an important component of plant defence, was also specific to the resistant cultivar at the transcriptome level. In addition, the inositol phosphate pathway was upregulated in the susceptible cultivar but downregulated in the resistant cultivar in response to S. subterranea infection. We provide large-scale multi-omics data of Spongospora-potato interaction and suggest an important role of glutathione metabolism in disease resistance.