Outbreaks of bacterially induced bleaching disease frequently occur in the commercially farmed seaweed Saccharina japonica during the nursery stage, which threatens the reliable supply of healthy sporelings. The use of disease resistant seaweed varieties is an effective and economic way to avoid disease outbreaks. Combining infection assay and transcriptome analyses, two representative S. japonica varieties, the main cultivated variety Sanhai and a newly developed variety Hainong No.1 were assessed for their susceptibility and defense responses to the bacterium Pseudoalteromonas piscicida X-8 (PpX-8) known to be a causative agent of seaweed bleaching disease. Compared with the sensitive Sanhai variety, PpX-8 infection assays with the Hainong No. 1 variety resulted in fewer bleached individuals and milder symptoms. Comparative transcriptome analysis after PpX-8 exposure showed that expression of genes related to defense responses occurs 2.5 h earlier in the Hainong No. 1 strain than the sensitive Sanhai variety. Differentially expressed genes, included genes encoding LRR protein, Serine/threonine-protein kinase CTR1, mannuronan C-5-epimerase, heat shock protein, antioxidases and transcriptional sir2 family. These results contribute to the understanding of the pathogen defensive strategies used by farmed S. japonica and will contribute to the development of disease resistant S. japonica varieties for commercial cultivation in the future.