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Explanation
The Joke
A man kneels and prays: "Dear Lord, why are we here?" He then asks: "Why did life begin on this plate? Why do we become?" A response comes (presumably from God or a scientist): "Our genetics calculated a date and time for arrival. We're marginal. Yet here we are." The man, stunned, asks: "God... is there a world beyond the dish?" -- revealing that the characters are bacteria living on a Petri dish. The final panel shows a scientist peering down at the dish, saying something about "a household free from tribulation."
The Humor
The comic uses a classic SMBC device: setting up what appears to be a profound theological conversation and then revealing it is happening on a completely different scale than the reader assumed. The "world," the "plate," the questions about the meaning of existence -- all of it turns out to be bacteria on a Petri dish asking existential questions about their tiny universe. The scientist looking down at the dish becomes a stand-in for God, unaware that the organisms are having a rich inner philosophical life. The humor comes from the absurd juxtaposition of grand existential questions with the mundane reality of microbiology, and from the implication that our own cosmic questions might look equally absurd to a being observing us from a larger scale.
References
The title "disc-world" is a nod to Terry Pratchett's Discworld series, where the world is a flat disc carried on the backs of four elephants standing on a giant turtle. Here, the "disc world" is literally a Petri dish. The comic also plays on the fine-tuning argument in theology -- the idea that the conditions for life are so precisely calibrated that they imply a designer -- by applying it to bacteria that were deliberately cultured by a scientist.