(Considerable discussion of sexual practices in this posting — largely in cautious language, but some may find the topics — male masturbation and male-male sexual acts — distasteful.)
To understand the brilliant 3/11 Wayno / Piraro Bizarro, you need to marshal detailed information about the Pillsbury Doughboy, the Roman Catholic confessional, the language of male masturbation in English, and self-rising flour (I wonder what, say, a Japanese exchange student in the U.S. would make of the cartoon; there is just so much culturally specific knowledge needed to understand it):
(#1) (If you’re puzzled by the odd symbols in the cartoon — Dan Piraro says there are 5 in this strip — see this Page.)
You must recognize the central figure as Poppin’ Fresh the Pillsbury Doughboy (though you can’t see the Pillsbury label on his chef’s hat), the dough-creature mascot of the (American) Pillsbury baking brand since 1965; and you must recognize that he’s at the grill, or screen, separating the penitent from the priest in the confessional box of a Roman Catholic Church, where he is confessing his sins (seeking absolution from the priest); then you must understand that the particular sin he’s confessing is masturbation (stimulating his penis by hand to become erect — to rise — for the purpose of sexual pleasure), and that this is a grave sin, requiring confession; and finally, and crucially, you have to see that his reference to his masturbating as self-rising (metonymically causing himself to rise) is a play on words, the ordinary use of self-rising being to flour (available mostly in the US and the UK) with added ingredients that will cause dough made from such flour to swell — to rise — on its own.
What makes the cartoon so delightful is that all of this is woven together by the fact that Poppin’ Fresh is an anthropomorphic being — a male one, with the desires of a sexually mature male — made of dough.